tbuckley/cabot-search huggingface dataset:
Surface display of functional moieties on extracellular vesicles using lipid anchors
Authors: Wenyi Zheng, Melanie Schürz, Rim Jawad Wiklander, Oskar Gustafsson, Dhanu Gupta, Radka Slovak, Andrei Traista, Arianna Coluzzi, Samantha Roudi, Antonella Barone, Daria Farcas, Eleni Kyriakopoulou, Valentina Galli, Heena Sharma, Nicole Meisner-Kober, Malgorzata Honcharenko, Samir E.L. Andaloussi
Journal: Journal of Controlled Release (2023)

Extracellular vesicles (EVs) are efficient natural vehicles for intercellular communication and are under extensive investigation for the delivery of diverse therapeutics including small molecule drugs, nucleic acids, and proteins. To understand the mechanisms behind the biological activities of EVs and develop EV therapeutics, it's fundamental to track EVs and engineer EVs in a customized manner. In this study, we identified, using single-vesicle flow cytometry and microscopy, the lipid DOPE (dioleoyl phosphatidyl ethanolamine) as an efficient anchor for isolated EVs. Notably, DOPE associated with EVs quickly, and the products remained stable under several challenging conditions. Moreover, conjugating fluorophores, receptor-targeting peptides or albumin-binding molecules with DOPE enabled tracking the cellular uptake, enhanceing the cellular uptake or extending the circulation time in mice of engineered EVs , respectively. Taken together, this study reports an efficient lipid anchor for exogenous engineering of EVs and further showcases its versatility for the functionalization of EVs.
Dissecting tumor lymphocyte infiltration to predict benefit from immune-checkpoint inhibitors in metastatic colorectal cancer: lessons from the AtezoT RIBE study
Authors: Roberto Moretto, Daniele Rossini, Aurélie Catteau, Carlotta Antoniotti, Mirella Giordano, Alessandra Boccaccino, Clara Ugolini, Agnese Proietti, Veronica Conca, Alboukadel Kassambara, Filippo Pietrantonio, Lisa Salvatore, Sara Lonardi, Stefano Tamberi, Emiliano Tamburini, Anello Marcello Poma, Jacques Fieschi, Gabriella Fontanini, Gianluca Masi, Jérôme Galon, Chiara Cremolini
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Tumor immune cells influence the efficacy of immune-checkpoint inhibitors (ICIs) and many efforts aim at identifying features of tumor immune microenvironment able to predict benefit from ICIs in proficient mismatch repair (pMMR)/microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Methods We characterized tumor immune cell infiltrate, by assessing tumor-infiltrating lymphocytes (TILs), Immunoscore, Immunoscore-IC, and programmed death ligand-1 (PD-L1) expression in tumor samples of patients with mCRC enrolled in the AtezoTRIBE study, a phase II randomized trial comparing FOLFOXIRI/bevacizumab/atezolizumab to FOLFOXIRI/bevacizumab, with the aim of evaluating the prognostic and predictive value of these features. Results Out of 218 patients enrolled, 181 (83%), 77 (35%), 157 (72%) and 162 (74%) specimens were successfully tested for TILs, Immunoscore, Immunoscore-IC and PD-L1 expression, respectively, and 69 (38%), 45 (58%), 50 (32%) and 21 (13%) tumors were classified as TILs-high, Immunoscore-high, Immunoscore-IC-high and PD-L1-high, respectively. A poor agreement was observed between TILs and Immunoscore or Immunoscore-IC (K of Cohen &lt;0.20). In the pMMR population, longer progression-free survival (PFS) was reported for Immunoscore-high and Immunoscore-IC-high groups compared with Immunoscore-low (16.4 vs 12.2 months; HR: 0.55, 95% CI: 0.30 to 0.99; p=0.049) and Immunoscore-IC-low (14.8 vs 11.5 months; HR: 0.55, 95% CI: 0.35 to 0.85; p=0.007), respectively, with a significant interaction effect between treatment arms and Immunoscore-IC (p for interaction: 0.006) and a trend for Immunoscore (p for interaction: 0.13). No PFS difference was shown according to TILs and PD-L1 expression. Consistent results were reported in the overall population. Conclusions The digital evaluation of tumor immune cell infiltrate by means of Immunoscore-IC or Immunoscore identifies the subset of patients with pMMR mCRC achieving more benefit from the addition of the anti-PD-L1 to the upfront treatment. Immunoscore-IC stands as the most promising predictor of benefit from ICIs.
Dual-stimulus phototherapeutic nanogel for triggering pyroptosis to promote cancer immunotherapy
Authors: Jiming Xu, Wei Qiu, Mengyun Liang, Mengjie Ye, Junfeng Hu, Xianbin Ma, Xiaoxiao Shi, Peng Xue, Yuejun Kang, Bo Xiao, Zhigang Xu
Journal: Journal of Controlled Release (2023)
Tips and tricks for endoscopic ultrasound-guided hepaticogastrostomy
Authors: Sardar M. Shah-Khan, Khaled Elfert, Avik Sarkar, Haroon Shahid, Amy Tyberg, Michel Kahaleh
Journal: Endoscopy (2023)

Endoscopic ultrasound-guided biliary drainage (EUS-BD) is a treatment option for patients with biliary obstruction in whom traditional endoscopic retrograde cholangiopancreatography (ERCP) is not possible due to altered upper gastrointestinal anatomy. In such cases, EUS-BD is a good alternative to surgery or percutaneous transhepatic biliary drainage (PTBD), with comparable clinical and technical success rates [1]. Two approaches have been described for EUS-guided transluminal biliary drainage. EUS-guided hepaticogastrostomy uses the transgastric approach and EUS-guided choledochoduodenostomy uses the transduodenal approach [2].
CasKAS: direct profiling of genome-wide dCas9 and Cas9 specificity using ssDNA mapping
Authors: Georgi K Marinov, Samuel H Kim, S Tansu Bagdatli, Soon Il Higashino, Alexandro E Trevino, Josh Tycko, Tong Wu, Lacramioara Bintu, Michael C Bassik, Chuan He, Anshul Kundaje, William J Greenleaf
Journal: Genome biology (2023)

Abstract Detecting and mitigating off-target activity is critical to the practical application of CRISPR-mediated genome and epigenome editing. While numerous methods have been developed to map Cas9 binding specificity genome-wide, they are generally time-consuming and/or expensive, and not applicable to catalytically dead CRISPR enzymes. We have developed CasKAS, a rapid, inexpensive, and facile assay for identifying off-target CRISPR enzyme binding and cleavage by chemically mapping the unwound single-stranded DNA structures formed upon binding of a sgRNA-loaded Cas9 protein. We demonstrate this method in both in vitro and in vivo contexts.
Oral spleen tyrosine kinase/Janus Kinase inhibitor gusacitinib for the treatment of chronic hand eczema: Results of a randomized phase 2 study
Authors: Pablo A. Jimenez, Howard L. Sofen, Robert Bissonnette, Mark Lee, Joseph Fowler, David J. Zammit, Yusong Chen, Niranjan Rao, Louis Denis, Sandeep Gupta
Journal: Journal of the American Academy of Dermatology (2023)

Gusacitinib is an oral inhibitor of Janus and Spleen tyrosine kinases.The efficacy and safety of gusacitinib were evaluated in a double-blind, placebo-controlled, multicenter, phase 2 study in 97 chronic hand eczema patients randomized (1:1:1) to placebo or gusacitinib (40 or 80 mg) for 12 weeks (part A). Then, in part B (through week 32), the patients received gusacitinib.At week 16, patients receiving 80 mg gusacitinib showed a 69.5% (P <.005) decrease in the modified total lesion-symptom score versus 49.0% for 40 mg (P =.132), and 33.5% for placebo. Considerable improvement in Physician's Global Assessment was seen in 31.3% of patients receiving 80 mg versus 6.3% of placebo (P <.05). A 73.3% decrease in the hand eczema severity index versus placebo (21.7%) occurred in patients receiving 80 mg (P <.001). Patients receiving 80 mg experienced a considerable decrease in hand pain (P <.05). As early as week 2, considerable reductions over placebo in modified total lesion-symptom score (P <.005), Physician's Global Assessment (P =.04), and hand eczema severity index (P <.01) were observed (80 mg gusacitinib). Adverse events included upper respiratory infection, headache, nausea, and nasopharyngitis.Gusacitinib showed rapid improvement in chronic hand eczema patients and was well tolerated, warranting further investigations.
STYLE (NCT03449173): A Phase 2 Trial of Sunitinib in Patients With Type B3 Thymoma or Thymic Carcinoma in Second and Further Lines
Authors: Claudia Proto, Sara Manglaviti, Giuseppe Lo Russo, Marco Musca, Giulia Galli, Martina Imbimbo, Matteo Perrino, Nadia Cordua, Eliana Rulli, Zelmira Ballatore, Alessandro Dal Maso, Antonio Chella, Andrea Sbrana, Arsela Prelaj, Roberto Ferrara, Mario Occhipinti, Marta Brambilla, Alessandro De Toma, Laura Mazzeo, Teresa Beninato, Diego Signorelli, Giacomo Massa, Francesca Gabriella Greco, Giuseppina Calareso, Daniela Miliziano, Rosa Maria Di Mauro, Giulia Mella, Alessandra Lucarelli, Angela Paggio, Francesca Galli, Valter Torri, Filippo Guglielmo Maria de Braud, Giulia Pasello, Iacopo Petrini, Rossana Berardi, Monica Ganzinelli, Marina Chiara Garassino, Paolo Andrea Zucali
Journal: Journal of Thoracic Oncology (2023)
Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines
Authors: Lijuan Xue, Keanqi Liu, Caixia Yan, Junling Dun, Yexin Xu, Linlin Wu, Huizhu Yang, Huafang Liu, Lin Xie, Guangji Wang, Yan Liang
Journal: Acta Pharmaceutica Sinica B (2023)

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.
Probable PTSD, PTSD symptom severity, and comorbid PTSD and hazardous drinking among sexual minority women compared to heterosexual women: A meta-analysis
Authors: Jillian R. Scheer, Emily C. Helminen, Cory J. Cascalheira, Virinca Jaipuriyar, Thomas J. Shaw, Sasha Zabelski, Kriti Behari, Sophia Pirog, Abigail W. Batchelder, Kyle Possemato, Tonda L. Hughes, Tami P. Sullivan
Journal: Clinical Psychology Review (2023)
Monomethyl branched-chain fatty acids: Health effects and biological mechanisms
Authors: Paulina Gozdzik, Faidon Magkos, Tomasz Sledzinski, Adriana Mika
Journal: Progress in Lipid Research (2023)

Branched-chain fatty acids (BCFA) are a group of lipids that are widely present in various organisms; they take part in numerous biochemical processes and affect multiple signaling pathways. However, BCFA are not well explored in terms of their effects on human health. Recently, they have been gaining interest, especially in relation to various human diseases. This review describes the occurrence of BCFA, their dietary sources, their potential health effects, and the current state of knowledge concerning their mechanism(s) of action. Many studies have been conducted so far in cellular and animal models, which reveal potent anti-cancer, lipid lowering, anti-inflammatory and neuroprotective actions. Research in humans is scarce. Therefore, further studies on animals and humans should be performed to confirm and expand these findings, and improve our understanding of the potential relevance of BCFA to human health and disease.
Cerebrovascular super-resolution 4D Flow MRI – Sequential combination of resolution enhancement by deep learning and physics-informed image processing to non-invasively quantify intracranial velocity, flow, and relative pressure
Authors: E. Ferdian, D. Marlevi, J. Schollenberger, M. Aristova, E.R. Edelman, S. Schnell, C.A. Figueroa, D.A. Nordsletten, A.A. Young
Journal: Medical Image Analysis (2023)
Macrophage transcription factor TonEBP promotes systemic lupus erythematosus and kidney injury via damage-induced signaling pathways
Authors: Eun Jin Yoo, Kook-Hwan Oh, Honglin Piao, Hyun Je Kang, Gyu Won Jeong, Hyun Park, Chang Jun Lee, Hyunjin Ryu, Seung Hee Yang, Myung-Gyu Kim, Dong Ki Kim, Sung Ho Park, Beom Jin Lim, Sang Min Lee, Chan Young Park, Soo Youn Choi, Whaseon Lee-Kwon, Jaeseok Yang, Hyug Moo Kwon
Journal: Kidney International (2023)

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by autoreactive B cells and dysregulation of many other types of immune cells including myeloid cells. Lupus nephritis (LN) is a common target organ manifestations of SLE. Tonicity-responsive enhancer-binding protein (TonEBP, also known as nuclear factor of activated T-cells 5 (NFAT5)), was initially identified as a central regulator of cellular responses to hypertonic stress and is a pleiotropic stress protein involved in a variety of immunometabolic diseases. To explore the role of TonEBP, we examined kidney biopsy samples from patients with LN. Kidney TonEBP expression was found to be elevated in these patients compared to control patients - in both kidney cells and infiltrating immune cells. Kidney TonEBP mRNA was elevated in LN and correlated with mRNAs encoding inflammatory cytokines and the degree of proteinuria. In a pristane-induced SLE model in mice, myeloid TonEBP deficiency blocked the development of SLE and LN. In macrophages, engagement of various toll-like receptors (TLRs) that respond to damage-associated molecular patterns induced TonEBP expression via stimulation of its promoter. Intracellular signaling downstream of the TLRs was dependent on TonEBP. Therefore, TonEBP can act as a transcriptional cofactor for NF-κB, and activated mTOR-IRF3/7 via protein-protein interactions. Additionally, TonEBP-deficient macrophages displayed elevated efferocytosis and animals with myeloid deficiency of TonEBP showed reduced Th1 and Th17 differentiation, consistent with macrophages defective in TLR signaling. Thus, our data show that myeloid TonEBP may be an attractive therapeutic target for SLE and LN.
Obesity-induced thymic involution and cancer risk
Authors: Maria K. Lagou, George S. Karagiannis
Journal: Seminars in Cancer Biology (2023)

Declining thymic functions associated either with old age (i.e., age-related thymic involution), or with acute involution as a result of stress, infectious disease, or cytoreductive therapies (e.g., chemotherapy/radiotherapy), have been associated with cancer development. A key mechanism underlying such increased cancer risk is the thymus-dependent debilitation of adaptive immunity, which is responsible for orchestrating immunoediting mechanisms and tumor immune surveillance. In the past few years, a blooming set of evidence has intriguingly linked obesity with cancer development and progression. The majority of such studies has focused on obesity-driven chronic inflammation, steroid/sex hormone and adipokine production, and hyperinsulinemia, as principal factors affecting the tumor microenvironment and driving the development of primary malignancy. However, experimental observations about the negative impact of obesity on T cell development and maturation have existed for more than half a century. Here, we critically discuss the molecular and cellular mechanisms of obesity-driven thymic involution as a previously underrepresented intermediary pathology leading to cancer development and progression. This knowledge could be especially relevant in the context of childhood obesity, because impaired thymic function in young individuals leads to immune system abnormalities, and predisposes to various pediatric cancers. A thorough understanding behind the molecular and cellular circuitries governing obesity-induced thymic involution could therefore help towards the rationalized development of targeted thymic regeneration strategies for obese individuals at high risk of cancer development.
Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study
Authors: Pierre-Henry Gabrielle, Marie-Noëlle Delyfer, Agnès Glacet-Bernard, Jean Baptiste Conart, Joel Uzzan, Laurent Kodjikian, Carl Arndt, Ramin Tadayoni, Agnès Soudry-Faure, Catherine P. Creuzot Garcher
Journal: Ophthalmology (2023)

To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm.Randomized, open-label, multicenter superiority study.Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (≤ 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium.Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 μg], and 20% sulfur hexafluoride [SF6] tamponade) or PD (0.05 ml intravitreal tPA [50 μg] and 0.3 ml intravitreal pure SF6). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up.The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up.Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7-24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1-25.7 letters]; adjusted difference β, 1.9 [-11.0; 14.9]; P = 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group.Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Prussian blue nanozymes coated with Pluronic attenuate inflammatory osteoarthritis by blocking c-Jun N-terminal kinase phosphorylation
Authors: Chanmi Cho, Hyeryeon Oh, Jin Sil Lee, Li-Jung Kang, Eun-Jeong Oh, Yiseul Hwang, Seok Jung Kim, Yong-Soo Bae, Eun-Jeong Kim, Ho Chul Kang, Won Il Choi, Siyoung Yang
Journal: Biomaterials (2023)

Osteoarthritis (OA) is a degenerative joint disorder associated with inflammation, functional disability, and high socioeconomic costs. The development of effective therapies against inflammatory OA has been limited owing to its complex and multifactorial nature. The efficacy of Prussian blue nanozymes coated with Pluronic (PPBzymes), US Food and Drug Administration-approved components, and their mechanisms of action have been described in this study, and PPBzymes have been characterized as a new OA therapeutic. Spherical PPBzymes were developed via nucleation and stabilization of Prussian blue inside Pluronic micelles. A uniformly distributed diameter of approximately 204 nm was obtained, which was maintained after storage in an aqueous solution and biological buffer. This indicates that PPBzymes are stable and could have biomedical applications. In vitro data revealed that PPBzymes promote cartilage generation and reduce cartilage degradation. Moreover, intra-articular injections with PPBzymes into mouse joints revealed their long-term stability and effective uptake into the cartilage matrix. Furthermore, intra-articular PPBzymes injections attenuated cartilage degradation without exhibiting cytotoxicity toward the synovial membrane, lungs, and liver. Notably, based on proteome microarray data, PPBzymes specifically block the JNK phosphorylation, which modulates inflammatory OA pathogenesis. These findings indicate that PPBzymes might represent a biocompatible and effective nanotherapeutic for obstructing JNK phosphorylation.
Update of European Society of Clinical Microbiology and Infectious Diseases coronavirus disease 2019 guidelines: diagnostic testing for severe acute respiratory syndrome coronavirus 2
Authors: Paraskevi C. Fragkou, Giulia De Angelis, Giulia Menchinelli, Fusun Can, Federico Garcia, Florence Morfin-Sherpa, Dimitra Dimopoulou, Konstantina Dimopoulou, Silvia Zelli, Adolfo de Salazar, Rieke Reiter, Hannah Janocha, Adriano Grossi, Jimmy Omony, Chrysanthi Skevaki
Journal: Clinical Microbiology and Infection (2023)